Financial Ties of Principal Investigators and Randomized Controlled Trial Outcomes: Cross Sectional Study

Overview

Journal BMJ

Specialty General Medicine

Date 2017 Jan 19

PMID 28096109

Citations 49

Authors

Rosa Ahn

Alexandra Woodbridge

Ann Abraham

Susan Saba

Deborah Korenstein

Erin Madden

W John Boscardin

Salomeh Keyhani

Affiliations

Soon will be listed here.

Abstract

Objective: To examine the association between the presence of individual principal investigators' financial ties to the manufacturer of the study drug and the trial's outcomes after accounting for source of research funding.

Design: Cross sectional study of randomized controlled trials (RCTs).

Setting: Studies published in "core clinical" journals, as identified by Medline, between 1 January 2013 and 31 December 2013.

Participants: Random sample of RCTs focused on drug efficacy.

Main Outcome Measure: Association between financial ties of principal investigators and study outcome.

Results: A total of 190 papers describing 195 studies met inclusion criteria. Financial ties between principal investigators and the pharmaceutical industry were present in 132 (67.7%) studies. Of 397 principal investigators, 231 (58%) had financial ties and 166 (42%) did not. Of all principal investigators, 156 (39%) reported advisor/consultancy payments, 81 (20%) reported speakers' fees, 81 (20%) reported unspecified financial ties, 52 (13%) reported honorariums, 52 (13%) reported employee relationships, 52 (13%) reported travel fees, 41 (10%) reported stock ownership, and 20 (5%) reported having a patent related to the study drug. The prevalence of financial ties of principal investigators was 76% (103/136) among positive studies and 49% (29/59) among negative studies. In unadjusted analyses, the presence of a financial tie was associated with a positive study outcome (odds ratio 3.23, 95% confidence interval 1.7 to 6.1). In the primary multivariate analysis, a financial tie was significantly associated with positive RCT outcome after adjustment for the study funding source (odds ratio 3.57 (1.7 to 7.7). The secondary analysis controlled for additional RCT characteristics such as study phase, sample size, country of first authors, specialty, trial registration, study design, type of analysis, comparator, and outcome measure. These characteristics did not appreciably affect the relation between financial ties and study outcomes (odds ratio 3.37, 1.4 to 7.9).

Conclusions: Financial ties of principal investigators were independently associated with positive clinical trial results. These findings may be suggestive of bias in the evidence base.

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References

Bekelman J, Li Y, Gross C . Scope and impact of financial conflicts of interest in biomedical research: a systematic review. JAMA. 2003; 289(4):454-65. DOI: 10.1001/jama.289.4.454. View

Bhandari M, Busse J, Jackowski D, Montori V, Schunemann H, Sprague S . Association between industry funding and statistically significant pro-industry findings in medical and surgical randomized trials. CMAJ. 2004; 170(4):477-80. PMC: 332713. View

Bodenheimer T . Uneasy alliance--clinical investigators and the pharmaceutical industry. N Engl J Med. 2000; 342(20):1539-44. DOI: 10.1056/NEJM200005183422024. View

Bariani G, de Celis Ferrari A, Hoff P, Krzyzanowska M, Riechelmann R . Self-reported conflicts of interest of authors, trial sponsorship, and the interpretation of editorials and related phase III trials in oncology. J Clin Oncol. 2013; 31(18):2289-95. DOI: 10.1200/JCO.2012.46.6706. View

Riechelmann R, Wang L, OCarroll A, Krzyzanowska M . Disclosure of conflicts of interest by authors of clinical trials and editorials in oncology. J Clin Oncol. 2007; 25(29):4642-7. DOI: 10.1200/JCO.2007.11.2482. View

Wang A, McCoy C, Murad M, Montori V . Association between industry affiliation and position on cardiovascular risk with rosiglitazone: cross sectional systematic review. BMJ. 2010; 340:c1344. PMC: 2841746. DOI: 10.1136/bmj.c1344. View

Opal S, Laterre P, Francois B, LaRosa S, Angus D, Mira J . Effect of eritoran, an antagonist of MD2-TLR4, on mortality in patients with severe sepsis: the ACCESS randomized trial. JAMA. 2013; 309(11):1154-62. DOI: 10.1001/jama.2013.2194. View

Anderson M, Chiswell K, Peterson E, Tasneem A, Topping J, Califf R . Compliance with results reporting at ClinicalTrials.gov. N Engl J Med. 2015; 372(11):1031-9. PMC: 4508873. DOI: 10.1056/NEJMsa1409364. View

Lexchin J . Those who have the gold make the evidence: how the pharmaceutical industry biases the outcomes of clinical trials of medications. Sci Eng Ethics. 2011; 18(2):247-61. DOI: 10.1007/s11948-011-9265-3. View

10.

Martinson B, Anderson M, De Vries R . Scientists behaving badly. Nature. 2005; 435(7043):737-8. DOI: 10.1038/435737a. View

11.

Matheson A . How industry uses the ICMJE guidelines to manipulate authorship--and how they should be revised. PLoS Med. 2011; 8(8):e1001072. PMC: 3153455. DOI: 10.1371/journal.pmed.1001072. View

12.

Aneja A, Esquitin R, Shah K, Iyengar R, Nisenbaum R, Melo M . Authors' self-declared financial conflicts of interest do not impact the results of major cardiovascular trials. J Am Coll Cardiol. 2013; 61(11):1137-43. DOI: 10.1016/j.jacc.2012.10.056. View

13.

Yaphe J, Edman R, Knishkowy B, Herman J . The association between funding by commercial interests and study outcome in randomized controlled drug trials. Fam Pract. 2001; 18(6):565-8. DOI: 10.1093/fampra/18.6.565. View

14.

Ridker P, Torres J . Reported outcomes in major cardiovascular clinical trials funded by for-profit and not-for-profit organizations: 2000-2005. JAMA. 2006; 295(19):2270-4. DOI: 10.1001/jama.295.19.2270. View

15.

Bauchner H . Editorial policies for clinical trials and the continued changes in medical journalism. JAMA. 2013; 310(2):149-50. DOI: 10.1001/jama.2013.8083. View

16.

Naci H, Ioannidis J . How good is "evidence" from clinical studies of drug effects and why might such evidence fail in the prediction of the clinical utility of drugs?. Annu Rev Pharmacol Toxicol. 2014; 55:169-89. DOI: 10.1146/annurev-pharmtox-010814-124614. View

17.

Perlis C, Harwood M, Perlis R . Extent and impact of industry sponsorship conflicts of interest in dermatology research. J Am Acad Dermatol. 2005; 52(6):967-71. DOI: 10.1016/j.jaad.2005.01.020. View

18.

Tereskerz P, Hamric A, Guterbock T, Moreno J . Prevalence of industry support and its relationship to research integrity. Account Res. 2009; 16(2):78-105. PMC: 2758529. DOI: 10.1080/08989620902854945. View

19.

Dwan K, Altman D, Arnaiz J, Bloom J, Chan A, Cronin E . Systematic review of the empirical evidence of study publication bias and outcome reporting bias. PLoS One. 2008; 3(8):e3081. PMC: 2518111. DOI: 10.1371/journal.pone.0003081. View

20.

Fontanarosa P, Flanagin A, DeAngelis C . Reporting conflicts of interest, financial aspects of research, and role of sponsors in funded studies. JAMA. 2005; 294(1):110-1. DOI: 10.1001/jama.294.1.110. View